Amorphous Computing

Amorphous computing is the development of organizational principles and programming languages for obtaining coherent behaviors from the cooperation of myriads of unreliable parts that are interconnected in unknown, irregular, and time-varying ways. The impetus for amorphous computing comes from developments in microfabrication and fundamental biology, each of which is the basis of a kernel technology that makes it possible to build or grow huge numbers of almost-identical information-processing units at almost no cost. This paper sets out a research agenda for realizing the potential of amorphous computing and surveys some initial progress, both in programming and in fabrication. We describe some approaches to programming amorphous systems, which are inspired by metaphors from biology and physics. We also present the basic ideas of cellular computing, an approach to constructing digital-logic circuits within living cells by representing logic levels by concentrations DNA-binding proteins

Effect of UV irradiation on Sulfolobus acidocaldarius and involvement of the general transcription factor TFB3 in the early UV response

Schult F, Lee TN, Albersmeier A, et al. Effect of UV irradiation on Sulfolobus acidocaldarius and involvement of the general transcription factor TFB3 in the early UV response. NUCLEIC ACIDS RESEARCH. 2018;46(14):7179-7192.Exposure to UV light can result in severe DNA damage. The alternative general transcription factor (GTF) TFB3 has been proposed to play a key role in the UV stress response in the thermoacidophilic crenarchaeon Sulfolobus acidocaldarius. Reporter gene assays confirmed that tfb3 is upregulated 90-180 min after UV treatment. In vivo tagging and immunodetection of TFB3 confirmed the induced expression at 90 min. Analysis of a tfb3 insertion mutant showed that genes encoding proteins of the Ups pili and the Ced DNA importer are no longer induced in a tfb3 insertion mutant after UV treatment, which was confirmed by aggregation assays. Thus, TFB3 plays a crucial role in the activation of these genes. Genome wide transcriptome analysis allowed a differentiation between a TFB3-dependent and a TFB3-independent early UV response. The TFB3-dependent UV response is characterized by the early induction of TFB3, followed by TFB3-dependent expression of genes involved in e.g. Ups pili formation and the Ced DNA importer. Many genes were downregulated in the tfb3 insertion mutant confirming the hypothesis that TFB3 acts as an activator of transcription. The TFB3-independent UV response includes the repression of nucleotide metabolism, replication and cell cycle progression in order to allow DNA repair

Statistics of 207 Lya Emitters at a Redshift Near 7: Constraints on Reionization and Galaxy Formation Models

We present Lya luminosity function (LF), clustering measurements, and Lya line profiles based on the largest sample, to date, of 207 Lya emitters (LAEs) at z=6.6 on the 1-deg^2 sky of Subaru/XMM-Newton Deep Survey (SXDS) field. Our z=6.6 Lya LF including cosmic variance estimates yields the best-fit Schechter parameters of phi*=8.5 +3.0/-2.2 x10^(-4) Mpc^(-3) and L*(Lya)=4.4 +/-0.6 x10^42 erg s^(-1) with a fixed alpha=-1.5, and indicates a decrease from z=5.7 at the >~90% confidence level. However, this decrease is not large, only =~30% in Lya luminosity, which is too small to be identified in the previous studies. A clustering signal of z=6.6 LAEs is detected for the first time. We obtain the correlation length of r_0=2-5 h^(-1) Mpc and bias of b=3-6, and find no significant boost of clustering amplitude by reionization at z=6.6. The average hosting dark halo mass inferred from clustering is 10^10-10^11 Mo, and duty cycle of LAE population is roughly ~1% albeit with large uncertainties. The average of our high-quality Keck/DEIMOS spectra shows an FWHM velocity width of 251 +/-16 km s^(-1). We find no large evolution of Lya line profile from z=5.7 to 6.6, and no anti-correlation between Lya luminosity and line width at z=6.6. The combination of various reionization models and our observational results about the LF, clustering, and line profile indicates that there would exist a small decrease of IGM's Lya transmission owing to reionization, but that the hydrogen IGM is not highly neutral at z=6.6. Our neutral-hydrogen fraction constraint implies that the major reionization process took place at z>~7.Comment: 28 pages, 23 figures. Accepted for publication in Ap

Cosmic Bell Test using Random Measurement Settings from High-Redshift Quasars

In this Letter, we present a cosmic Bell experiment with polarization-entangled photons, in which measurement settings were determined based on real-time measurements of the wavelength of photons from high-redshift quasars, whose light was emitted billions of years ago, the experiment simultaneously ensures locality. Assuming fair sampling for all detected photons and that the wavelength of the quasar photons had not been selectively altered or previewed between emission and detection, we observe statistically significant violation of Bell's inequality by $9.3$ standard deviations, corresponding to an estimated $p$ value of $\lesssim 7.4 \times 10^{-21}$. This experiment pushes back to at least $\sim 7.8$ Gyr ago the most recent time by which any local-realist influences could have exploited the "freedom-of-choice" loophole to engineer the observed Bell violation, excluding any such mechanism from $96\%$ of the space-time volume of the past light cone of our experiment, extending from the big bang to today.Comment: 9 pages, 4 figures, plus Supplemental Material (16 pages, 8 figures). Matches version to be published in Physical Review Letter

Phenotype-specific effect of chromosome 1q21.1 rearrangements and GJA5 duplications in 2436 congenital heart disease patients and 6760 controls

Recurrent rearrangements of chromosome 1q21.1 that occur via non-allelic homologous recombination have been associated with variable phenotypes exhibiting incomplete penetrance, including congenital heart disease (CHD). However, the gene or genes within the ∼1 Mb critical region responsible for each of the associated phenotypes remains unknown. We examined the 1q21.1 locus in 948 patients with tetralogy of Fallot (TOF), 1488 patients with other forms of CHD and 6760 ethnically matched controls using single nucleotide polymorphism genotyping arrays (Illumina 660W and Affymetrix 6.0) and multiplex ligation-dependent probe amplification. We found that duplication of 1q21.1 was more common in cases of TOF than in controls [odds ratio (OR) 30.9, 95% confidence interval (CI) 8.9-107.6); P = 2.2 × 10−7], but deletion was not. In contrast, deletion of 1q21.1 was more common in cases of non-TOF CHD than in controls [OR 5.5 (95% CI 1.4-22.0); P = 0.04] while duplication was not. We also detected rare (n = 3) 100-200 kb duplications within the critical region of 1q21.1 in cases of TOF. These small duplications encompassed a single gene in common, GJA5, and were enriched in cases of TOF in comparison to controls [OR = 10.7 (95% CI 1.8-64.3), P = 0.01]. These findings show that duplication and deletion at chromosome 1q21.1 exhibit a degree of phenotypic specificity in CHD, and implicate GJA5 as the gene responsible for the CHD phenotypes observed with copy number imbalances at this locu

Pump it Up workshop report

Workshop held 28-29 September 2017, Cape Cod, MAA two-day workshop was conducted to trade ideas and brainstorm about how to advance our understanding of the ocean’s biological pump. The goal was to identify the most important scientific issues that are unresolved but might be addressed with new and future technological advances

Phenotype-specific effect of chromosome 1q21.1 rearrangements and GJA5 duplications in 2436 congenital heart disease patients and 6760 controls

Recurrent rearrangements of chromosome 1q21.1 that occur via non-allelic homologous recombination have been associated with variable phenotypes exhibiting incomplete penetrance, including congenital heart disease (CHD). However, the gene or genes within the ∼1 Mb critical region responsible for each of the associated phenotypes remains unknown. We examined the 1q21.1 locus in 948 patients with tetralogy of Fallot (TOF), 1488 patients with other forms of CHD and 6760 ethnically matched controls using single nucleotide polymorphism genotyping arrays (Illumina 660W and Affymetrix 6.0) and multiplex ligation-dependent probe amplification. We found that duplication of 1q21.1 was more common in cases of TOF than in controls [odds ratio (OR) 30.9, 95% confidence interval (CI) 8.9–107.6); P = 2.2 × 10−7], but deletion was not. In contrast, deletion of 1q21.1 was more common in cases of non-TOF CHD than in controls [OR 5.5 (95% CI 1.4–22.0); P = 0.04] while duplication was not. We also detected rare (n = 3) 100–200 kb duplications within the critical region of 1q21.1 in cases of TOF. These small duplications encompassed a single gene in common, GJA5, and were enriched in cases of TOF in comparison to controls [OR = 10.7 (95% CI 1.8–64.3), P = 0.01]. These findings show that duplication and deletion at chromosome 1q21.1 exhibit a degree of phenotypic specificity in CHD, and implicate GJA5 as the gene responsible for the CHD phenotypes observed with copy number imbalances at this locus

Genome-wide association study identifies loci on 12q24 and 13q32 associated with Tetralogy of Fallot

We conducted a genome-wide association study to search for risk alleles associated with Tetralogy of Fallot (TOF), using a northern European discovery set of 835 cases and 5159 controls. A region on chromosome 12q24 was associated (P = 1.4 × 10−7) and replicated convincingly (P = 3.9 × 10−5) in 798 cases and 2931 controls [per allele odds ratio (OR) = 1.27 in replication cohort, P = 7.7 × 10−11 in combined populations]. Single nucleotide polymorphisms in the glypican 5 gene on chromosome 13q32 were also associated (P = 1.7 × 10−7) and replicated convincingly (P = 1.2 × 10−5) in 789 cases and 2927 controls (per allele OR = 1.31 in replication cohort, P = 3.03 × 10−11 in combined populations). Four additional regions on chromosomes 10, 15 and 16 showed suggestive association accompanied by nominal replication. This study, the first genome-wide association study of a congenital heart malformation phenotype, provides evidence that common genetic variation influences the risk of TO

(Mis-)Interpreting supernovae observations in a lumpy universe

Light from `point sources' such as supernovae is observed with a beam width of order of the sources' size - typically less than 1 AU. Such a beam probes matter and curvature distributions that are very different from coarse-grained representations in N-body simulations or perturbation theory, which are smoothed on scales much larger than 1 AU. The beam typically travels through unclustered dark matter and hydrogen with a mean density much less than the cosmic mean, and through dark matter halos and hydrogen clouds. Using N-body simulations, as well as a Press-Schechter approach, we quantify the density probability distribution as a function of beam width and show that, even for Gpc-length beams of 500 kpc diameter, most lines of sight are significantly under-dense. From this we argue that modelling the probability distribution for AU-diameter beams is absolutely critical. Standard analyses predict a huge variance for such tiny beam sizes, and nonlinear corrections appear to be non-trivial. It is not even clear whether under-dense regions lead to dimming or brightening of sources, owing to the uncertainty in modelling the expansion rate which we show is the dominant contribution. By considering different reasonable approximations which yield very different cosmologies we argue that modelling ultra-narrow beams accurately remains a critical problem for precision cosmology. This could appear as a discordance between angular diameter and luminosity distances when comparing SN observations to BAO or CMB distances.Comment: 20 pages and 6 figures. v3 is a substantially revised version, now including detailed analysis of N-body and Press-Schechter predictions which indicate that even for 1Gpc/h length beams, the mean density sampled is significantly below the cosmic mea

The global status of insect resistance to neonicotinoid insecticides

This document is the Accepted Manuscript version of the following article: Chris Bass, Ian Denholm, Martin S. Williamson, and Ralf Nauen, ‘The global status of insect resistance to neonicotinoid insecticides’, Pesticide Biochemistry and Physiology, Vol. 121, pp. 78-87, June 2015. The Version of Record is available online at doi: https://doi.org/10.1016/j.pestbp.2015.04.004. Published by Elsevier Copyright © 2015 Elsevier Inc.The first neonicotinoid insecticide, imidacloprid, was launched in 1991. Today this class of insecticides comprises at least seven major compounds with a market share of more than 25% of total global insecticide sales. Neonicotinoid insecticides are highly selective agonists of insect nicotinic acetylcholine receptors and provide farmers with invaluable, highly effective tools against some of the world's most destructive crop pests. These include sucking pests such as aphids, whiteflies, and planthoppers, and also some coleopteran, dipteran and lepidopteran species. Although many insect species are still successfully controlled by neonicotinoids, their popularity has imposed a mounting selection pressure for resistance, and in several species resistance has now reached levels that compromise the efficacy of these insecticides. Research to understand the molecular basis of neonicotinoid resistance has revealed both target-site and metabolic mechanisms conferring resistance. For target-site resistance, field-evolved mutations have only been characterized in two aphid species. Metabolic resistance appears much more common, with the enhanced expression of one or more cytochrome P450s frequently reported in resistant strains. Despite the current scale of resistance, neonicotinoids remain a major component of many pest control programmes, and resistance management strategies, based on mode of action rotation, are of crucial importance in preventing resistance becoming more widespread. In this review we summarize the current status of neonicotinoid resistance, the biochemical and molecular mechanisms involved, and the implications for resistance management.Peer reviewedFinal Accepted Versio